Head and neck squamous cell carcinomas (SCCHN) have one of the highest frequencies of gene amplification in human cancers. Amplification of chromosomal band 11q13 is observed in approximately 45 percent of SCCHN (compared to approximately 15-25 percent of other carcinomas) and is associated with a poor prognosis. The literature has focused on cyclin D1 (CCND1) and cortactin (EMS1) driving amplification and tumor progression. However, our preliminary data indicate that seven, not two genes within the 11q13 amplicon are overexpressed. We hypothesize that the overexpression of multiple genes in 11q13 contributes to tumor progression. To test this, we propose to 1) determine which genes are overexpressed in SCCHN cell lines and primary tumors with and without amplification and 2) test the effects on gene expression and cellular phenotype of a) knockdown of the overexpression of specific genes and gene combinations using small interfering RNA (siRNA), and b) overexpression if specific genes and gene combinations in normal cells. This study can then be extended to other tumor types with 11q13 amplification, leading to a better understanding of the biology of disease, more accurate diagnostic tools, and possibly, targeted therapies. [unreadable] [unreadable] [unreadable]